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A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC
This study has been completed.
Sponsors and Collaborators: Upjohn
National Institute of Allergy and Infectious Diseases (NIAID)
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000753
  Purpose

To determine the safety, toxicity, pharmacokinetic profile, and antiretroviral activity of atevirdine mesylate ( U-87201E ) in HIV-infected patients. Per 06/04/93 amendment, to also evaluate the interactive effects of didanosine ( ddI ) or zalcitabine ( dideoxycytidine; ddC ) with zidovudine ( AZT ) on the pharmacokinetics of U-87201E and to assess the effects of the triple combination therapies on immunologic and virologic parameters.

Since the use of non-nucleoside reverse transcriptase inhibitors such as U-87201E has been associated with the rapid development of resistant HIV isolates, an initial evaluation of this drug in patients was made in combination with AZT. Because of the inability to detect resistance after 6 weeks of combined AZT/U-87201E therapy, this protocol will initially investigate U-87201E administered alone and then investigate the effect of this drug with AZT and ddI or ddC.


Condition Intervention Phase
HIV Infections
Drug: Atevirdine mesylate
Drug: Zidovudine
Drug: Zalcitabine
Drug: Didanosine
Phase I

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Didanosine Zalcitabine Atevirdine Atevirdine mesylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: A Phase I Concentration-Targeted Multidose Study of Atevirdine Mesylate ( U-87201E ), AZT, and ddI or ddC

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 30
Detailed Description:

Since the use of non-nucleoside reverse transcriptase inhibitors such as U-87201E has been associated with the rapid development of resistant HIV isolates, an initial evaluation of this drug in patients was made in combination with AZT. Because of the inability to detect resistance after 6 weeks of combined AZT/U-87201E therapy, this protocol will initially investigate U-87201E administered alone and then investigate the effect of this drug with AZT and ddI or ddC.

Ten patients are treated at each of three targeted concentration ranges of U-87201E. Patients in the second cohort are enrolled immediately after patients in the first cohort are accrued; patients in the third cohort are enrolled when 5 of 10 patients in the second cohort have tolerated that dose for at least 4 weeks. The MTD will be the dose below that which produces dose-limiting grade 3 or 4 toxicity in five out of 10 patients. At least two women and five antiretroviral naive patients must be enrolled in each dose concentration range. Patients receive at least 8 weeks of monotherapy with U-87201E, with possible extension to at least 24 weeks with the same dose of U-87201E alone or in combination with zidovudine plus either ddI or ddC. Patients are followed weekly for at least 8 weeks and, if applicable, at weeks 10, 12, 16, 20, and 24 and monthly thereafter, up to 1 month following the last dose. Patients on combination therapy will have an indwelling venous catheter inserted for the first 2 days of combination therapy. Per 10/15/93 amendment, if no MTD is established with the first three cohorts, then 10 additional patients will be enrolled at a fourth concentration.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • PCP prophylaxis with pentamidine, TMP/SMX, or dapsone (if appropriate).
  • Clotrimazole troches or nystatin oral suspension for oral candidiasis.
  • Acyclovir (up to 1000 mg/day) for herpes lesions.
  • Supportive care as deemed necessary for toxicities .

Patients must have:

  • HIV infection.
  • CD4 count <= 500 cells/mm3.
  • No active opportunistic infections.
  • Consent of parent, guardian, or person with power of attorney, if less than 18 years of age.

NOTE:

  • Participation of women in the study is encouraged.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Acute medical problems, including opportunistic infections (e.g., active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, and CMV) or nonopportunistic diseases (e.g., liver or renal disease or lymphoma).
  • Current diagnosis of malignancy for which systemic therapy would be required during the study.
  • Active gastrointestinal disorders.

Concurrent Medication:

Excluded:

  • Investigational drugs.
  • Systemic therapy for malignancy.
  • Phenobarbital, phenytoin, ketoconazole, rifampin, rifabutin, cimetidine, beta blockers, chronic antacids, antiarrhythmic agents, or other medications known to affect cardiac conduction or seizure threshold.

Patients with the following prior conditions are excluded:

  • History of any cardiovascular disease, including conduction disturbances, arrhythmias or atherosclerotic heart disease.
  • History of CNS disease such as seizure disorder, AIDS Dementia Complex, progressive multifocal leukoencephalopathy, or any other active neurological disorder.
  • History of chronic gastrointestinal disorders such as chronic diarrhea (> 4 weeks duration).

Prior Medication:

Excluded:

  • Antiretroviral or immunomodulator agents (such as AZT, ddI, ddC, interferon, etc.) within 15 days prior to study entry.
  • Cytotoxic chemotherapy within 1 month prior to study entry.
  • Prior U-87201E or other non-nucleoside reverse transcriptase inhibitors (i.e., nevirapine, TIBO, L697,661).

Present use of alcohol or illicit drugs.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000753

Locations
United States, California
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 900331079
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
Upjohn
Glaxo Wellcome
Investigators
Study Chair: Reichman R
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Zalcitabine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: ACTG 187
Study First Received: November 2, 1999
Last Updated: July 29, 2008
ClinicalTrials.gov Identifier: NCT00000753  
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zalcitabine
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Didanosine
HIV Infections
Zalcitabine
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009